[unreadable] [unreadable] Duke University Medical Center, East Carolina University (ECU), and Wake Forest University Health Systems (WFUHS) have formed the North Carolina Consortium (NCC) to participate in Pediatric Heart Disease Network trials and studies. Our three Institutions have collaborated since 1996 in over 48 projects with funding of approximately 56 million dollars. Over 90% of the over 300 patients with congenital heart defects who undergo open heart surgery at our Centers are followed in our clinics annually. Our patient population is unique: our patients are ethnically and racially diverse, poor, and rural. The challenges and unique strengths encountered by our patients are likely to affect outcomes measured in clinical trials. These effects must be identified to generalize the results of PHN clinical trials to encompass the patient population across the United States. We propose a randomized, multi-Institutional, double-blind, placebo-controlled study to evaluate the effect of spironolactone on exercise performance in children who have undergone Fontan surgery: aldosterone blockade and exercise (ABLE). Hypothesis: Spironolactone will improve the exercise performance and quality of life of Fontan patients, 6-21 years of age. Primary objective: Determine the effect of spironolactone on peak oxygen consumption. Secondary Objectives: determine efficacy of spironolactone as measured by 1) quality of life, assessed by validated measures; 2) ventricular filling parameters, assessed by tissue Doppler echocardiography; 3) amount of myocardial scarring assessed by MRI; 4) neurohormonal activation, BNP; biomarkers of collagen synthesis, procollagen I and III peptides; and 5) renin angiotensin aldosterone system polymorphisms. The trial duration is six months. A sample size of 220 per treatment group will be required to achieve 85% statistical power to detect mean differences in peak oxygen consumption between spironolactone and placebo, using a two-sided test without alpha = 0.05, if the expected mean difference in peak oxygen consumption between groups is 2 ml/kg/min and the standard deviation within the group is 7 ml/kg/min. The proposed study is significant and innovative: the results may support a new therapy; it will be the largest randomized study to date of pharmacologic treatment of children with single ventricle physiology; potential mechanisms through which aldosterone antagonism affects these children will be assessed; the role of RAAS polymorphisms in these children's response to pharmacologic therapy will be evaluated. We are also applying for a Clinical Research Skills Development Core. (End of Abstract). [unreadable] [unreadable] [unreadable]